2od9
From Proteopedia
(New page: 200px<br /><applet load="2od9" size="450" color="white" frame="true" align="right" spinBox="true" caption="2od9, resolution 2.05Å" /> '''Structural Basis for...) |
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| - | [[Image:2od9.gif|left|200px]]<br /><applet load="2od9" size=" | + | [[Image:2od9.gif|left|200px]]<br /><applet load="2od9" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2od9, resolution 2.05Å" /> | caption="2od9, resolution 2.05Å" /> | ||
'''Structural Basis for Nicotinamide Inhibition and Base Exchange in Sir2 Enzymes'''<br /> | '''Structural Basis for Nicotinamide Inhibition and Base Exchange in Sir2 Enzymes'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The Sir2 family of proteins consists of broadly conserved NAD(+)-dependent | + | The Sir2 family of proteins consists of broadly conserved NAD(+)-dependent deacetylases that are implicated in diverse biological processes, including DNA regulation, metabolism, and longevity. Sir2 proteins are regulated in part by the cellular concentrations of a noncompetitive inhibitor, nicotinamide, that reacts with a Sir2 reaction intermediate via a base-exchange reaction to reform NAD(+) at the expense of deacetylation. To gain a mechanistic understanding of nicotinamide inhibition in Sir2 enzymes, we captured the structure of nicotinamide bound to a Sir2 homolog, yeast Hst2, in complex with its acetyl-lysine 16 histone H4 substrate and a reaction intermediate analog, ADP-HPD. Together with related biochemical studies and structures, we identify a nicotinamide inhibition and base-exchange site that is distinct from the so-called "C pocket" binding site for the nicotinamide group of NAD(+). These results provide insights into the Sir2 mechanism of nicotinamide inhibition and have important implications for the development of Sir2-specific effectors. |
==About this Structure== | ==About this Structure== | ||
| - | 2OD9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with ZN, A1R and NCA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2OD9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=A1R:'>A1R</scene> and <scene name='pdbligand=NCA:'>NCA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OD9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Marmorstein, R.]] | [[Category: Marmorstein, R.]] | ||
| - | [[Category: Sanders, B | + | [[Category: Sanders, B D.]] |
[[Category: A1R]] | [[Category: A1R]] | ||
[[Category: NCA]] | [[Category: NCA]] | ||
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[[Category: zn binding protein]] | [[Category: zn binding protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:17:06 2008'' |
Revision as of 16:17, 21 February 2008
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Structural Basis for Nicotinamide Inhibition and Base Exchange in Sir2 Enzymes
Overview
The Sir2 family of proteins consists of broadly conserved NAD(+)-dependent deacetylases that are implicated in diverse biological processes, including DNA regulation, metabolism, and longevity. Sir2 proteins are regulated in part by the cellular concentrations of a noncompetitive inhibitor, nicotinamide, that reacts with a Sir2 reaction intermediate via a base-exchange reaction to reform NAD(+) at the expense of deacetylation. To gain a mechanistic understanding of nicotinamide inhibition in Sir2 enzymes, we captured the structure of nicotinamide bound to a Sir2 homolog, yeast Hst2, in complex with its acetyl-lysine 16 histone H4 substrate and a reaction intermediate analog, ADP-HPD. Together with related biochemical studies and structures, we identify a nicotinamide inhibition and base-exchange site that is distinct from the so-called "C pocket" binding site for the nicotinamide group of NAD(+). These results provide insights into the Sir2 mechanism of nicotinamide inhibition and have important implications for the development of Sir2-specific effectors.
About this Structure
2OD9 is a Single protein structure of sequence from Saccharomyces cerevisiae with , and as ligands. Full crystallographic information is available from OCA.
Reference
Structural basis for nicotinamide inhibition and base exchange in Sir2 enzymes., Sanders BD, Zhao K, Slama JT, Marmorstein R, Mol Cell. 2007 Feb 9;25(3):463-72. PMID:17289592
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